Journal
ANDROLOGIA
Volume 53, Issue 5, Pages -Publisher
WILEY
DOI: 10.1111/and.14016
Keywords
Akt; doxorubicin; miR‐ 21; PI3K; prostate cancer; PTEN
Categories
Funding
- Central Hospital
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The study showed that suppression of miR-21 significantly reduced cell viability of PC3/DOX, downregulated P-gp expression and activity in DOX-resistant cells, and reversed MDR by increasing the intracellular accumulation of DOX in PC3/DOX cells. Additionally, miR-21 repression led to the upregulation of PTEN and subsequently lower expression of P-gp, enhancing the apoptosis rate of PC3/DOX cells. The findings contribute to the understanding of the role of miR-21 in reversing MDR in prostate cancer.
Many approaches have been examined to reversing multidrug resistance (MDR), but sub-optimal target-based strategies have limited their efficacy. Herein, we investigate microRNA (miR-21) suppression on the doxorubicin (DOX)-sensitisation of the DOX-resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR-21, P-glycoprotein (P-gp), MDR-1 and PTEN evaluated in PC3/DOX cancer cells by qRT-PCR and western blot analyses. The cytotoxic effects of transfected of miR-21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P-gp. Apoptosis was detected by Flow cytometry. As expected, miR-21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA-21 suppression considerably hindered PC3/DOX cell viability. miR-21 suppression dramatically downregulated P-gp expression and activity in DOX-resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P-gp cascade, which miR-21 suppression led to the upregulation of PTEN and sequentially lower-expression of P-gp that reversed MDR. Also, miR-21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR-21 in MDR-reversing in PCa.
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